Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DTKNH2D)

• DTP Name: Sodium/glucose cotransporter 2 (SLC5A2)
• Gene Name: SLC5A2
• UniProt ID: P31639 (SC5A2_HUMAN)
• VARIDT ID: DTD0422
• Synonyms: Low affinity sodium-glucose cotransporter; Na(+)/glucose cotransporter 2; SGLT2; SLC5A2; Solute carrier family 5 member 2
• DTP Family: Solute:Sodium Symporter (SSS) Family
• Sequence:
  MEEHTEAGSAPEMGAQKALIDNPADILVIAAYFLLVIGVGLWSMCRTNRGTVGGYFLAGR
  SMVWWPVGASLFASNIGSGHFVGLAGTGAASGLAVAGFEWNALFVVLLLGWLFAPVYLTA
  GVITMPQYLRKRFGGRRIRLYLSVLSLFLYIFTKISVDMFSGAVFIQQALGWNIYASVIA
  LLGITMIYTVTGGLAALMYTDTVQTFVILGGACILMGYAFHEVGGYSGLFDKYLGAATSL
  TVSEDPAVGNISSFCYRPRPDSYHLLRHPVTGDLPWPALLLGLTIVSGWYWCSDQVIVQR
  CLAGKSLTHIKAGCILCGYLKLTPMFLMVMPGMISRILYPDEVACVVPEVCRRVCGTEVG
  CSNIAYPRLVVKLMPNGLRGLMLAVMLAALMSSLASIFNSSSTLFTMDIYTRLRPRAGDR
  ELLLVGRLWVVFIVVVSVAWLPVVQAAQGGQLFDYIQAVSSYLAPPVSAVFVLALFVPRV
  NEQGAFWGLIGGLLMGLARLIPEFSFGSGSCVQPSACPAFLCGVHYLYFAIVLFFCSGLL
  TLTVSLCTAPIPRKHLHRLVFSLRHSKEEREDLDADEQQGSSLPVQNGCPESAMEMNEPQ
  APAPSLFRQCLLWFCGMSRGGVGSPPPLTQEEAAAAARRLEDISEDPSWARVVNLNALLM
  MAVAVFLWGFYA
• Function: This sodium-dependent transporter mediate the transport of glucose.
• Endogenous Substrate(s): D-glucose
• TCDB ID: 2.A.21.3.16
• Gene ID: 6524
• Reactome Pathway:
  Defective SLC5A2 causes renal glucosuria (GLYS1) (R-HSA-5658208)
  Cellular hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DTP

1 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-glucose	DMMG2TO	Discovery agent	N.A.	Investigative	[17]

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	8.64E-01	3.98E-02	1.64E-01
Adrenocortical carcinoma	2D11.Z	Kidney	5.13E-01	-7.11E-02	-2.74E-01
Alopecia	ED70	Skin from scalp	4.81E-01	1.21E-02	3.47E-02
Alzheimer's disease	8A20	Entorhinal cortex	4.50E-01	-8.37E-03	-6.37E-02
Ankylosing spondylitis	FA92.0	Pheripheral blood	8.25E-01	1.90E-02	1.34E-01
Aortic stenosis	BB70	Calcified aortic valve	7.48E-01	1.04E-01	1.78E-01
Apnea	7A40	Hyperplastic tonsil	9.24E-01	-5.87E-02	-2.24E-01
Arthropathy	FA00-FA5Z	Peripheral blood	9.36E-01	7.18E-03	4.43E-02
Asthma	CA23	Nasal and bronchial airway	1.30E-01	-2.63E-02	-6.82E-02
Atopic dermatitis	EA80	Skin	3.76E-02	5.30E-02	3.61E-01
Autism	6A02	Whole blood	7.23E-02	-6.63E-02	-2.38E-01
Autoimmune uveitis	9A96	Peripheral monocyte	4.69E-01	3.31E-04	1.63E-03
Autosomal dominant monocytopenia	4B04	Whole blood	7.01E-01	-4.45E-02	-4.20E-01
Bacterial infection of gingival	1C1H	Gingival tissue	4.81E-05	1.68E-01	6.47E-01
Batten disease	5C56.1	Whole blood	1.71E-01	2.53E-02	3.33E-01
Behcet's disease	4A62	Peripheral blood	1.15E-01	7.41E-02	4.18E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	9.24E-01	-1.32E-02	-8.83E-02
Bladder cancer	2C94	Bladder tissue	1.16E-05	5.39E-01	3.71E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.24E-02	-4.70E-02	-1.48E-01
Cardioembolic stroke	8B11.20	Whole blood	1.93E-08	-3.62E-01	-1.58E+00
Cervical cancer	2C77	Cervical tissue	7.65E-01	2.89E-02	1.44E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	9.82E-01	1.07E-01	3.42E-01
Chronic hepatitis C	1E51.1	Whole blood	3.34E-01	4.03E-02	3.13E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	3.47E-01	1.03E-01	4.66E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.04E-01	4.46E-02	1.78E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	6.08E-02	7.50E-02	9.79E-01
Colon cancer	2B90	Colon tissue	5.19E-11	-1.51E-01	-6.89E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.34E-01	-3.89E-01	-7.16E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	2.30E-01	-2.16E-01	-8.67E-01
Endometriosis	GA10	Endometrium tissue	4.93E-01	2.65E-03	1.55E-02
Familial hypercholesterolemia	5C80.00	Peripheral blood	6.70E-01	-2.25E-02	-1.06E-01
Familial hypercholesterolemia	5C80.00	Whole blood	3.44E-04	-3.70E-01	-1.02E+00
Gastric cancer	2B72	Gastric tissue	6.34E-01	6.62E-02	7.33E-01
Glioblastopma	2A00.00	Nervous tissue	3.46E-26	-1.42E-01	-6.71E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	8.68E-01	4.08E-02	1.03E-01
Head and neck cancer	2D42	Head and neck tissue	1.23E-02	7.00E-02	3.22E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	1.56E-01	-4.58E-02	-2.41E-01
Huntington's disease	8A01.10	Whole blood	1.67E-01	1.45E-01	6.93E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	9.94E-01	-1.79E-02	-1.21E-01
Immunodeficiency	4A00-4A20	Peripheral blood	8.26E-02	-8.66E-02	-8.90E-01
Influenza	1.00E+30	Whole blood	2.22E-01	8.13E-02	5.88E-01
Interstitial cystitis	GC00.3	Bladder tissue	6.83E-03	2.36E-01	5.32E+00
Intracranial aneurysm	8B01.0	Intracranial artery	6.82E-01	5.97E-02	2.50E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.80E-01	-1.03E-01	-2.73E-01
Ischemic stroke	8B11	Peripheral blood	3.88E-02	9.77E-02	5.11E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.75E-11	-4.38E-01	-1.27E+00
Lateral sclerosis	8B60.4	Cervical spinal cord	8.94E-01	-5.08E-02	-3.89E-01
Lateral sclerosis	8B60.4	Skin	4.87E-01	-6.13E-02	-4.82E-01
Liver cancer	2C12.0	Liver tissue	4.49E-04	-1.36E-01	-5.36E-01
Liver failure	DB99.7-DB99.8	Liver tissue	1.42E-02	3.06E-01	1.83E+00
Lung cancer	2C25	Lung tissue	5.14E-01	-1.02E-02	-4.70E-02
Lupus erythematosus	4A40	Whole blood	7.02E-03	-6.20E-02	-1.53E-01
Major depressive disorder	6A70-6A7Z	Whole blood	4.61E-01	-9.43E-02	-3.46E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	3.58E-01	3.55E-02	2.47E-01
Melanoma	2C30	Skin	5.90E-01	-4.46E-02	-7.82E-02
Multiple myeloma	2A83.1	Bone marrow	4.24E-01	-3.56E-02	-1.89E-01
Multiple myeloma	2A83.1	Peripheral blood	9.22E-01	-3.02E-02	-1.14E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	3.87E-01	5.50E-02	3.12E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.58E-01	9.07E-02	5.35E-01
Myelofibrosis	2A20.2	Whole blood	3.24E-01	-8.60E-02	-5.01E-01
Myocardial infarction	BA41-BA50	Peripheral blood	1.25E-01	-2.43E-01	-3.95E-01
Myopathy	8C70.6	Muscle tissue	9.31E-02	-6.33E-02	-4.02E-01
Neonatal sepsis	KA60	Whole blood	2.42E-01	-3.67E-02	-1.09E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	6.02E-03	-4.51E-01	-1.38E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	6.81E-01	-6.40E-02	-3.26E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.23E-01	9.35E-02	5.84E-01
Olive pollen allergy	CA08.00	Peripheral blood	2.78E-01	1.81E-01	5.84E-01
Oral cancer	2B6E	Oral tissue	1.91E-06	-3.12E-01	-1.26E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	1.70E-01	-7.71E-02	-2.86E-01
Osteoporosis	FB83.1	Bone marrow	3.63E-02	3.19E-01	7.80E+00
Ovarian cancer	2C73	Ovarian tissue	5.86E-01	-1.24E-01	-8.05E-01
Pancreatic cancer	2C10	Pancreas	4.00E-03	-6.31E-01	-1.28E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	2.65E-01	-9.18E-02	-4.53E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	6.18E-01	7.43E-02	4.51E-01
Pituitary cancer	2D12	Pituitary tissue	3.96E-02	2.72E-01	7.85E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	7.45E-02	1.44E-01	4.99E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	8.60E-01	-5.62E-02	-3.31E-01
Polycythemia vera	2A20.4	Whole blood	3.74E-02	1.75E-03	1.02E-02
Pompe disease	5C51.3	Biceps muscle	3.56E-02	-1.02E-01	-3.90E-01
Preterm birth	KA21.4Z	Myometrium	7.09E-01	4.70E-02	4.62E-01
Prostate cancer	2C82	Prostate	2.71E-04	8.43E-01	1.27E+00
Psoriasis	EA90	Skin	3.18E-02	5.85E-02	1.37E-01
Rectal cancer	2B92	Rectal colon tissue	3.37E-02	-2.02E-01	-1.35E+00
Renal cancer	2C90-2C91	Kidney	1.88E-03	-1.21E+00	-1.62E+00
Retinoblastoma	2D02.2	Uvea	4.35E-03	-2.98E-01	-1.78E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.26E-01	-4.56E-02	-1.08E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	7.16E-01	5.14E-03	4.37E-02
Schizophrenia	6A20	Prefrontal cortex	3.84E-02	2.79E-02	1.27E-01
Schizophrenia	6A20	Superior temporal cortex	4.26E-01	-1.08E-02	-1.33E-01
Scleroderma	4A42.Z	Whole blood	6.43E-01	8.00E-02	4.48E-01
Seizure	8A60-8A6Z	Whole blood	2.49E-01	-1.32E-01	-6.04E-01
Sensitive skin	EK0Z	Skin	6.67E-01	-1.64E-01	-9.08E-01
Sepsis with septic shock	1G41	Whole blood	8.89E-01	1.03E-02	3.02E-02
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.64E-01	1.38E-01	5.10E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	6.00E-01	7.47E-05	2.31E-04
Simpson golabi behmel syndrome	LD2C	Adipose tissue	3.53E-01	-1.51E-01	-1.12E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	2.88E-01	-3.25E-01	-1.11E+00
Skin cancer	2C30-2C3Z	Skin	1.51E-06	-1.90E-01	-4.78E-01
Thrombocythemia	3B63	Whole blood	2.93E-01	6.22E-02	3.28E-01
Thrombocytopenia	3B64	Whole blood	6.20E-01	2.62E-01	2.07E-01
Thyroid cancer	2D10	Thyroid	3.13E-05	1.48E-01	6.45E-01
Tibial muscular dystrophy	8C75	Muscle tissue	1.30E-03	-2.37E-01	-1.42E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	1.14E-01	1.55E-01	1.67E+00
Type 2 diabetes	5A11	Liver tissue	3.26E-01	-8.69E-02	-3.68E-01
Ureter cancer	2C92	Urothelium	4.24E-02	-4.16E-02	-2.45E-01
Uterine cancer	2C78	Endometrium tissue	6.06E-01	3.02E-02	1.19E-01
Vitiligo	ED63.0	Skin	1.21E-01	-1.17E-01	-4.22E-01

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Sodium/glucose cotransporter 2 (SGLT2) DTT Info
• DTP DTT Type: Successful

6 Approved Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Canagliflozin	DMFRM1I	Non-insulin dependent diabetes	5A11	Approved	[1]
Dapagliflozin	DM28UJG	Non-insulin dependent diabetes	5A11	Approved	[2]
Dapagliflozin Propanediol; Saxagliptin Hydrochloride	DM34TXO	Type-2 diabetes	5A11	Approved	[3]
Empagliflozin	DMRF9YK	Type-1 diabetes	5A10	Approved	[2]
PF-04971729	DM79VXT	Type-2 diabetes	5A11	Approved	[4]
Sotagliflozin	DMMLXA9	Heart failure	BD10-BD13	Approved	[5]

9 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP1941	DMGQ1TV	Liver disease	DB90-BD99	Phase 3	[6]
AVE-2268	DMA42BV	Diabetic complication	5A2Y	Phase 2	[7]
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[8]
Remogliflozin etabonate	DMW4YK1	Type-1/2 diabetes	5A10-5A11	Phase 2	[9]
RO-4998452	DMZJREM	Type-2 diabetes	5A11	Phase 2	[10]
YG1699	DM1NR1J	Type-1 diabetes	5A10	Phase 2	[11]
YM-543	DMRZBPI	Type-2 diabetes	5A11	Phase 2	[12]
BI-44847	DM2KVM0	Type-2 diabetes	5A11	Phase 1	[13]
EGT-0001474	DMDPGCS	Type-2 diabetes	5A11	Phase 1	[14]

1 Discontinued Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TS-033	DMALIFO	Diabetic complication	5A2Y	Discontinued in Phase 2	[15]

2 Investigative Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Empagli ozin	DMQLNZC	Type-2 diabetes	5A11	Investigative	[2]
sergliflozin	DMF8GAX	Discovery agent	N.A.	Investigative	[16]

References

• [1] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [2] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin.Diabetes Obes Metab.2015 Jun;17(6):591-8.
• [5] LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69.
• [6] Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan.World J Diabetes.2015 Feb 15;6(1):136-44.
• [7] Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats. Arzneimittelforschung. 2008;58(11):574-80.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.Diabetes Obes Metab.2015 Oct;17(10):984-93.
• [11] ClinicalTrials.gov (NCT04956263) A Comparison of Postprandial Glucose After a Mixed Meal Tolerance Test, and the Metabolic Effects of Insulin Withdrawal in a Crossover Study of the Dual Systemic SGLT1 and SGLT2 Inhibitor YG1699, and the Selective SGLT2 Inhibitor Dapagliflozin in Subjects With Type 1 Diabetes. U.S.National Institutes of Health.
• [12] Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor. Endocr Res. 2013 Aug;38(3):168-183.
• [13] Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes
• [14] PhRMA report
• [15] Company report (Taisho)
• [16] Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal gluco... J Pharmacol Exp Ther. 2007 Jan;320(1):323-30.
• [17] The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS One. 2014 Feb 26;9(2):e89977.